Ch3 Chronic Inflammation and Tissue Repair EC Flashcards
Primary leukocytes of chronic inflammation
Monocytes/macrophages
Also lymphocytes, plasma cells, eosinophils
Granulation tissue
Blood vessels and fibroblasts
Precursor to scar formation
Fibronectin required
Fibronectin
Key adhesion glycoprotein of ECM
Chemotactic factor for fibroblasts and endothelial cells
Examples of caseating granulomas
TB Systemic fungi (histo)
Examples of non-caseating granulomas
Sarcoidosis
Crohn’s
Cell types in infectious granuloma
Activated macrophages (epitheliod cells - fuse to form multinucleated giant cells) Th1 CD4 cells TNF-alpha necessary for maintenance of granuloma (TNF-alpha inhibitors can result in systemic TB)
Regulation of the G1 to S checkpoint
p53 inhibits Cdk4 phosphorylation of RB, which allows cell to enter S phase
How does p53 induce apoptosis in cells in which the DNA is damaged?
Inhibits translocation of BCL-2 (usually antiapoptotic)
Inhibits translocation of MYC (growth promoting)
VEGF
Stimulates angiogenesis
Stimulated by TNF and hypoxia
FGF
Chemotactic for fibroblasts
Stimulates keratinocyte migration, angiogenesis, and wound contraction
EGF
Stimulates keratinocyte migration and granulation tissue formation
PDGF
Chemotactic, and angiogenesis
TGF-beta
Chemotactic for macrophages, lymphocytes, fibroblasts, and angiogenesis
IL-1
Stimulates synthesis of metalloproteinases
Stimulates synthesis and release of acute phase reactant proteins
TNF
Activates macrophages
Stimulates release of acute phase reactants
What is the initial collagen in wound repair?
Type III collagen -poor tensile strength
Function of metalloproteinases
Contain Zinc
Convert Type III collagen to Type I
Wound strength 80% original after 3 months
What is the most common cause of impaired healing? What is the most common pathogen?
Infection
S. aureus
MRSA mechanism of path
Produce Panton-Valentine leukocidin which accelerates PMN apoptosis
May progress to necrotizing fasciitis
How does diabetes mellitus increase susceptibility to infection?
Decreased blood flow
Increased tissue glucose (bug food)
How do nutritional deficiencies impair wound healing?
Malnutrition (decreased protein) Vit. C/ Copper deficiency (decreased collagen cross linking) Zinc deficiency (defects in removal of type III collagen
How do glucocorticoids impair wound healing?
Prevent scar formation by interfering with collagen formation and decrease tensile strength
plastic surgeons inject steroids into wounds to prevent scar formation
Keloids
Raised scars extending beyond borders of original wound
bundles in same plane as epidermis
Hypertrophic scar
Raised scar remaining in confines of original wound
bundles in same plane as epidermis